Virus Genetics Flashcards

1
Q

Types of virus genomes

A
  • DNA or RNA but not both
  • single or double stranded
  • single stranded RNA can be segmented or nonsegmented
  • linear or circular
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2
Q

Size of viruses

A
  • Parvoviruses- 2 genes
  • Retroviruses- 3 genes
  • Papillonaviruses- about 8 genes
  • Adenoviruses- about 10 genes
  • Herpes viruses- 70 genes and more
  • Pox viruses- 200 genes

viruses have too few genes to survive independently, and depend on cellular genes to supply the missing functions

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3
Q

Gene expression in viruses

A
  • regulated by cellular transcription factors

- Papillomavirus gene expression is regulated by keratinocyte factors, thus making the virus skin specific

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4
Q

Viruses are efficient

A
  • no space is wasted
  • 100 percent of genome encoding protein or tRNA
  • reading frames can overlap
  • ribosomal frame shifting- known as translational frameshifts, due to ribosome slipping 1 or 2 bases on RNA
  • alternative splicing of RNA
  • cleavage of polyproteins by viral proteases (drug target)
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5
Q

Genome structures

A
  • simple genomes- Retrovirus- genes linear on one RNA strand, with one promoter
  • complex genomes- adenoviruses, herpesviruses, poxviruses- genes on both strands of DNA, often over lapping and each with its own promoter
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6
Q

Virus high mutation frequency

A
  • high error rate of polymerase
  • lack of proofreading and error correction
  • lack of second strand in some viruses

-all types of mutations: point mutations, deletions, insertions, recombinations and rearrangements, insertion to host cell genome

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7
Q

Virus mutations

A
  • allow epidermiological studies
  • can allow live vaccines to be made
  • can produce new antigens which avoid immunity
  • can lead to drug resistance
  • integration of viral genome can cause disease
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8
Q

Complementation

A

when a gene function of one virus replaces a mutated gene of another. Allows defective viruses to replicate and express their genes. Allows cell lines to support vaccine productio

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9
Q

Phenotype mixing of similar viruses

A
  • exchange of capsid proteins

- if two polio virus serotypes infect the same cell the progeny might have capsids that are a mix of each serotype

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10
Q

Pseudotype virus

A

-the genetic material of one virus in the capsid or envelop of another

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11
Q

Recombination of homologous viruses

A

-the exchange of genes by crossing over at regions of homology. Produces a hybrid virus which reproduces- Western equine encephalitis virus

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12
Q

Reassortment of segmented viral genomes

A
  • the rearrangement of parts of a segmented genome to form a new set of segments
  • eg infuenza virus- antigenic shift
  • reovirus (adenovirus)
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13
Q

Virus interference

A
  • infection by one virus tends to prevent infection by another by:
  • blocking of receptors
  • competition for resources
  • production of interferon or other anti-viral agents
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14
Q

Viral insertion mutations

A

-when a virus inserts like HIV it can interrupt the normal host genome and affect transcription in this way too

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15
Q

Development of Gene Therapy Viruses

A
  • deletion of essential gene- insert that gene into packaging cell
  • clone the therapeutic gene to virus
  • grow the virus in the packaging cell
  • test in cells- animals- humans
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16
Q

Diseases that might be treated by gene therapy

A
  • hemophilia
  • immune deficiencies
  • retinal disorders
  • liver enzymes deficiencies
  • cystic fibrosis
  • cancer: tumor suppressor genes, silencing of oncogenes, immune response genes, toxic or suicide genes, replicating cytotoxic viruses
17
Q

Delivery of gene therapy by certain viruses

A

-delivery of gene therapy by viruses requires mutants whose replication is severely restricted
-they can be made from:
Retroviruses (mouse viruses, or HIV)
Adenoviruses
Herpes Simplex Virus
Adeno-associated virus

18
Q

Problems with gene therapy

A
  • short/ transient expression of foreign gene
  • low efficiency of gene transfer
  • inflammation in response to the virus- requirement for very high doses of virus vectors
  • potential for chromosomal disturbances by virus
19
Q

Gene therapy virus side effects

A
  • Jesse Gelsinger- ornithine transcarbamylase deficiency, clinical trial with OTC in adenovirus into hepatic artery, developed acute respiratory distress syndrome
  • Jolee Mohr, adalimumab, AAV/TNF blocker into knee died of systemic histoplasmosis
  • SCID-X1, mouse leukemia virus modified to transduce stem cells, some developed T cell leukemia
20
Q

Future research on gene therapy

A
  • mutated viruses that cause less imflammation
  • viruses that target a specific tissue
  • conditionally replicating viruses
  • non-viral methods of transfer of genes